Genetic DNA profile in urine and hair follicles from patients who have undergone allogeneic hematopoietic stem cell transplantation.

Biological samples from patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) constitute a challenge for individual identification. In this study we analyzed the genetic profiles (by the amplification of 15 autosomic STRs) of HSCT patients found in different types of samples (blood, hair and urine) that may be the source of DNA in civil or criminal forensic cases. Our results show that while in hair follicles the donor component was not detected in any patient, thus being a reliable source of biological material for forensic identification, mixed chimerism was detected in urine samples from all patient, and no correlation was found between the time elapsed from the transplant and the percentage of chimerism. These results certainly have practical implications if the urine is being considered as a source of DNA for identification purposes in HSTC patients. Moreover, taking into consideration that chimerism was found not only in patients with leukocyturia (given the hematopoietic origin of leukocytes, this was expected), but also in those without observable leukocytes in the sediment, we conclude that an alternative source or sources of donor DNA must be implicated.

Experience with anidulafungin in patients with allogeneic hematopoietic stem cell transplantation and graft-versus-host disease.

BACKGROUND: It is well known that both acute and chronic graft-versus-host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment. METHODS: We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD - grade III-IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and "overlap" GVHD (n = 3) - who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD. RESULTS: Twenty-one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6-17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively. CONCLUSIONS: Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.

Validation of models with constant bias: an applied approach / Validación de modelos con sesgo constante: un enfoque aplicado

Objective. This paper presents extensions to the statistical validation method based on the procedure of Freese when a model shows constant bias (CB) in its predictions and illustrate the method with data from a new mechanistic model that predict weight gain in cattle. Materials and methods. The extensions were the hypothesis tests and maximum anticipated error for the alternative approach, and the confidence interval for a quantile of the distribution of errors. Results. The model evaluated showed CB, once the CB is removed and with a confidence level of 95%, the magnitude of the error does not exceed 0.575 kg. Therefore, the validated model can be used to predict the daily weight gain of cattle, although it will require an adjustment in its structure based on the presence of CB to increase the accuracy of its forecasts. Conclusions. The confidence interval for the 1-α quantile of the distribution of errors after correcting the constant bias, allows determining the top limit for the magnitude of the error of prediction and use it to evaluate the evolution of the model in the forecasting of the system. The confidence interval approach to validate a model is more informative than the hypothesis tests for the same purpose.

Objetivo. Presentar extensiones al método estadístico para validar modelos basado en el procedimiento de Freese cuando el modelo presenta sesgo constante (SC) en sus predicciones e ilustrar el método con datos provenientes de un modelo mecanístico inédito para la predicción de ganancia de peso de bovinos. Materiales y métodos. Las extensiones fueron la prueba de hipótesis y error máximo anticipado para el planteamiento alternativo y el intervalo de confianza para un cuantil de la distribución de los errores. Resultados. El modelo evaluado presentó SC, una vez eliminado y con un nivel de confianza del 95%, la magnitud del error no sobrepasa 0.575 kg. Por lo que el modelo validado puede usarse para predecir la ganancia de peso diaria de bovinos, aunque requerirá un ajuste en su estructura con base a la presencia de SC para incrementar la exactitud en sus pronósticos. Conclusiones. El intervalo de confianza para el cuantil 1-α de la distribución de los errores una vez que se corrige el sesgo constante, permite determinar una cota superior para la magnitud del error de predicción y usarla para evaluar la evolución del modelo en predicción del sistema. El enfoque de intervalos de confianza para validar un modelo es más informativo que las pruebas de hipótesis para el mismo propósito.

Evaluation of the sensitivity of two recently developed STR multiplexes for the analysis of chimerism after haematopoietic stem cell transplantation.

Forensic-oriented kits analysing short tandem repeat (STR) polymorphisms are widely used to determine the proportions of donor and recipient cells after haematopoietic stem cell transplantation. The sensitivity of this technology is crucial for the early detection of relapse and, in consequence, the adjustment of the treatment to enhance donor-origin haematopoiesis in transplant recipients. The objective of this study was to compare the performance of two recently developed STR multiplex kits, AmpFℓSTR(®) Identifiler(®) Plus PCR Amplification Kit (Applied Biosystems) and Investigator™ IDplex(®) (Qiagen), in the analysis of chimerism. Fifteen STR loci were amplified with both kits in 26 peripheral blood samples of transplantated patients showing chimerism. Peak amplitude threshold, detection limit (%DL), per cent donor chimerism and efficacy of each multiplex and STR were determined, and the results with both kits were compared. The %DL and the estimated per cent donor chimerism were similar with both kits. On the other hand, Identifiler(®) Plus kit allowed chimerism identification only in 24 (92%) of the 26 cases with chimerism detected by using the Investigator™ IDplex(®) when only 'type 5' allelic constellations (i.e. without potential interference by stutter peaks) were taken into account. However, IDplex(®) efficacy was somewhat lower than that of Identifiler Plus when only the most informative loci (D2S1338, D21S11, D18S51 and FGA) were considered. Therefore, although each system had some particular advantages and disadvantages, overall both STR multiplexes showed similar performance in qualitative and quantitative chimerism analysis.

Ecografía en rehabilitación / Ultrasonography in rehabilitation

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